Response of a ferrofluid to traveling-stripe forcing

We observe the dynamics of waves propagating on the surface of a ferrofluid under the influence of a spatially and temporarily modulated field. In particular, we excite plane waves by a travelling lamellar modulation of the magnetization. By this external driving both the wavelength and the propagation velocity of the waves can be controlled. The amplitude of the excited waves exhibits a resonance phenomenon similar to that of a forced harmonic oscillator. Its analysis reveals the dispersion relation of the free surface waves, from which the critical magnetic field for the onset of the Rosensweig instability can be extrapolated

Progress in Three-Dimensional Coherent X-Ray Diffraction Imaging

The Fourier inversion of phased coherent diffraction patterns offers images without the resolution and depth-of-focus limitations of lens-based tomographic systems. We report on our recent experimental images inverted using recent developments in phase retrieval algorithms, and summarize efforts that led to these accomplishments. These include ab-initio reconstruction of a two-dimensional test pattern, infinite depth of focus image of a thick object, and its high-resolution (~10 nm resolution) three-dimensional image. Developments on the structural imaging of low density aerogel samples are discussed.Comment: 5 pages, X-Ray Microscopy 2005, Himeji, Japa

High-resolution ab initio three-dimensional X-ray diffraction microscopy

Coherent X-ray diffraction microscopy is a method of imaging non-periodic isolated objects at resolutions only limited, in principle, by the largest scattering angles recorded. We demonstrate X-ray diffraction imaging with high resolution in all three dimensions, as determined by a quantitative analysis of the reconstructed volume images. These images are retrieved from the 3D diffraction data using no a priori knowledge about the shape or composition of the object, which has never before been demonstrated on a non-periodic object. We also construct 2D images of thick objects with infinite depth of focus (without loss of transverse spatial resolution). These methods can be used to image biological and materials science samples at high resolution using X-ray undulator radiation, and establishes the techniques to be used in atomic-resolution ultrafast imaging at X-ray free-electron laser sources.Comment: 22 pages, 11 figures, submitte

Coherent X-ray Diffractive Imaging; applications and limitations

The inversion of a diffraction pattern offers aberration-free diffraction-limited 3D images without the resolution and depth-of-field limitations of lens-based tomographic systems, the only limitation being radiation damage. We review our experimental results, discuss the fundamental limits of this technique and future plans.Comment: 7 pages, 8 figure

Biallelic variants in ADARB1, encoding a dsRNA-specific adenosine deaminase, cause a severe developmental and epileptic encephalopathy

Background Adenosine-to-inosine RNA editing is a co-transcriptional/post-transcriptional modification of double-stranded RNA, catalysed by one of two active adenosine deaminases acting on RNA (ADARs), ADAR1 and ADAR2. ADARB1 encodes the enzyme ADAR2 that is highly expressed in the brain and essential to modulate the function of glutamate and serotonin receptors. Impaired ADAR2 editing causes early onset progressive epilepsy and premature death in mice. In humans, ADAR2 dysfunction has been very recently linked to a neurodevelopmental disorder with microcephaly and epilepsy in four unrelated subjects. Methods We studied three children from two consanguineous families with severe developmental and epileptic encephalopathy (DEE) through detailed physical and instrumental examinations. Exome sequencing (ES) was used to identify ADARB1 mutations as the underlying genetic cause and in vitro assays with transiently transfected cells were performed to ascertain the impact on ADAR2 enzymatic activity and splicing. Results All patients showed global developmental delay, intractable early infantile-onset seizures, microcephaly, severe-to-profound intellectual disability, axial hypotonia and progressive appendicular spasticity. ES revealed the novel missense c.1889G>A, p.(Arg630Gln) and deletion c.1245_1247+1 del, p.(Leu415PhefsTer14) variants in ADARB1 (NM_015833.4). The p.(Leu415PhefsTer14) variant leads to incorrect splicing resulting in frameshift with a premature stop codon and loss of enzyme function. In vitro RNA editing assays showed that the p.(Arg630Gln) variant resulted in a severe impairment of ADAR2 enzymatic activity. Conclusion In conclusion, these data support the pathogenic role of biallelic ADARB1 variants as the cause of a distinctive form of DEE, reinforcing the importance of RNA editing in brain function and development

Prevalence of Fabry Disease among Patients with Parkinson's Disease

BACKGROUND: An increased prevalence of Parkinson’s disease (PD) disease has been previously reported in subjects with Fabry disease (FD) carrying alpha-galactosidase (GLA) mutations and their first-line relatives. Moreover, decreased alpha-galactosidase A (AGLA) enzymatic activity has been reported among cases with PD compared to controls. OBJECTIVE: The aim of our study was to determine the prevalence of FD among patients with PD. METHODS: We recruited 236 consecutive patients with PD from February 2018 to December 2020. Clinical and sociodemographic data, including the MDS-UPDRS-III scores and HY stage (the Hoehn and Yahr scale), were collected, and in-depth phenotyping was performed in subjects with identified GLA variants. A multistep approach, including standard determination of AGLA activity and LysoGb3 in males, and next-generation based GLA sequencing in all females and males with abnormal AGLA levels was performed in a routine diagnostic setting. RESULTS: The mean age of our patients was 68.9 ± 8.9 years, 130 were men (55.1%), and the mean disease duration was 7.77 ± 5.35 years. Among 130 men, AGLA levels were low in 20 patients (15%), and subsequent Lyso-Gb3 testing showed values within the reference range for all tested subjects. In 126 subsequently genetically tested patients, four heterozygous p.(Asp313Tyr) GLA variants (3.2%, MAF 0.016) were identified; all were females. None of the 4 GLA variant carriers identified had any clinical manifestation suggestive of FD. CONCLUSIONS: The results of this study suggest a possible relationship between FD and PD in a small proportion of cases. Nevertheless, the GLA variant found in our cohort is classified as a variant of unknown significance. Therefore, its pathogenic causative role in the context of PD needs further elucidation, and these findings should be interpreted with caution

Biallelic variants in ADARB1, encoding a dsRNA-specific adenosine deaminase, cause a severe developmental and epileptic encephalopathy

Background: Adenosine-to-inosine RNA editing is a co-transcriptional/post-transcriptional modification of double-stranded RNA, catalysed by one of two active adenosine deaminases acting on RNA (ADARs), ADAR1 and ADAR2. ADARB1 encodes the enzyme ADAR2 that is highly expressed in the brain and essential to modulate the function of glutamate and serotonin receptors. Impaired ADAR2 editing causes early onset progressive epilepsy and premature death in mice. In humans, ADAR2 dysfunction has been very recently linked to a neurodevelopmental disorder with microcephaly and epilepsy in four unrelated subjects. / Methods: We studied three children from two consanguineous families with severe developmental and epileptic encephalopathy (DEE) through detailed physical and instrumental examinations. Exome sequencing (ES) was used to identify ADARB1 mutations as the underlying genetic cause and in vitro assays with transiently transfected cells were performed to ascertain the impact on ADAR2 enzymatic activity and splicing. / Results: All patients showed global developmental delay, intractable early infantile-onset seizures, microcephaly, severe-to-profound intellectual disability, axial hypotonia and progressive appendicular spasticity. ES revealed the novel missense c.1889G>A, p.(Arg630Gln) and deletion c.1245_1247+1 del, p.(Leu415PhefsTer14) variants in ADARB1 (NM_015833.4). The p.(Leu415PhefsTer14) variant leads to incorrect splicing resulting in frameshift with a premature stop codon and loss of enzyme function. In vitro RNA editing assays showed that the p.(Arg630Gln) variant resulted in a severe impairment of ADAR2 enzymatic activity. / Conclusion: In conclusion, these data support the pathogenic role of biallelic ADARB1 variants as the cause of a distinctive form of DEE, reinforcing the importance of RNA editing in brain function and development

Biallelic variants in ADARB1, encoding a dsRNA-specific adenosine deaminase, cause a severe developmental and epileptic encephalopathy.

BACKGROUND: Adenosine-to-inosine RNA editing is a co-transcriptional/post-transcriptional modification of double-stranded RNA, catalysed by one of two active adenosine deaminases acting on RNA (ADARs), ADAR1 and ADAR2. ADARB1 encodes the enzyme ADAR2 that is highly expressed in the brain and essential to modulate the function of glutamate and serotonin receptors. Impaired ADAR2 editing causes early onset progressive epilepsy and premature death in mice. In humans, ADAR2 dysfunction has been very recently linked to a neurodevelopmental disorder with microcephaly and epilepsy in four unrelated subjects. METHODS: We studied three children from two consanguineous families with severe developmental and epileptic encephalopathy (DEE) through detailed physical and instrumental examinations. Exome sequencing (ES) was used to identify ADARB1 mutations as the underlying genetic cause and in vitro assays with transiently transfected cells were performed to ascertain the impact on ADAR2 enzymatic activity and splicing. RESULTS: All patients showed global developmental delay, intractable early infantile-onset seizures, microcephaly, severe-to-profound intellectual disability, axial hypotonia and progressive appendicular spasticity. ES revealed the novel missense c.1889G>A, p.(Arg630Gln) and deletion c.1245_1247+1 del, p.(Leu415PhefsTer14) variants in ADARB1 (NM_015833.4). The p.(Leu415PhefsTer14) variant leads to incorrect splicing resulting in frameshift with a premature stop codon and loss of enzyme function. In vitro RNA editing assays showed that the p.(Arg630Gln) variant resulted in a severe impairment of ADAR2 enzymatic activity. CONCLUSION: In conclusion, these data support the pathogenic role of biallelic ADARB1 variants as the cause of a distinctive form of DEE, reinforcing the importance of RNA editing in brain function and development

A new density variance - Mach number relation for subsonic and supersonic, isothermal turbulence

The probability density function (PDF) of the gas density in subsonic and supersonic, isothermal, driven turbulence is analyzed with a systematic set of hydrodynamical grid simulations with resolutions up to 1024^3 cells. We performed a series of numerical experiments with root mean square (r.m.s.) Mach number M ranging from the nearly incompressible, subsonic (M=0.1) to the highly compressible, supersonic (M=15) regime. We study the influence of two extreme cases for the driving mechanism by applying a purely solenoidal (divergence-free) and a purely compressive (curl-free) forcing field to drive the turbulence. We find that our measurements fit the linear relation between the r.m.s. Mach number and the standard deviation of the density distribution in a wide range of Mach numbers, where the proportionality constant depends on the type of the forcing. In addition, we propose a new linear relation between the standard deviation of the density distribution and the standard deviation of the velocity in compressible modes, i.e. the compressible component of the r.m.s. Mach number. In this relation the influence of the forcing is significantly reduced, suggesting a linear relation between the standard deviation of the density distribution and the standard deviation of the velocity in compressible modes, independent of the forcing, ranging from the subsonic to the supersonic regime.Comment: 8 pages,6 figures, The Astrophysical Journal (submitted

The impact of late treatment-toxicity on generic health-related quality of life in head and neck cancer patients after radiotherapy

SummaryTo examine the impact of late treatment-related xerostomia and dysphagia on health-related quality of life (HRQOL) in head and neck cancer (HNC) patients after radiotherapy. A multi-center cross-sectional survey was performed. Patients with a follow-up of at least 6months after curative radiotherapy, without evidence of recurrent disease were eligible for inclusion. The Euroqol-5D questionnaire (EQ-5D) was filled out and toxicity was scored and converted to the RTOG scale. The EQ-5D measures generic HRQOL in terms of utility and visual analogue scale (VAS) scores. Missing data on the EQ-5D were imputed using multiple imputation. HRQOL was compared between subgroups of patients with and without toxicity. Subsequently, the impact of xerostomia and dysphagia on HRQOL was analyzed using multivariate regression analyses. Both analyses were performed separately for utility scores and VAS scores. The study population was composed of 396 HNC patients. The average utility and VAS scores were 0.85 (scale 0–1) and 75 (scale 0–100). Subgroups of patients with xerostomia and/or dysphagia showed statistically significantly lower utility and VAS scores (P=0.000–0.022). The multivariate regression model showed that xerostomia and dysphagia were negative predictors of both utility and VAS scores. Other factors which influenced HRQOL in at least one of the two regression models were: sex, tumor location and the addition of surgery to radiotherapy. Xerostomia and dysphagia diminish generic HRQOL. Moreover dysphagia affects patients’ HRQOL stronger than xerostomia